Transforming growth factor-β signalling in tumour resistance to the anti-PD-(L)1 therapy: Updated.

Low frequency of durable responses in patients treated with immune checkpoint inhibitors (ICIs) demands for taking complementary strategies in order to boost immune responses against cancer. Transforming growth factor-β (TGF-β) is a multi-tasking cytokine that is frequently expressed in tumours and acts as a critical promoter of tumour hallmarks. TGF-β promotes an immunosuppressive tumour microenvironment (TME) and defines a bypass mechanism to the ICI therapy. A number of cells within the stroma of tumour are influenced from TGF-β activity. There is also evidence of a relation between TGF-β with programmed death-ligand 1 (PD-L1) expression within TME, and it influences the efficacy of anti-programmed death-1 receptor (PD-1) or anti-PD-L1 therapy. Combination of TGF-β inhibitors with anti-PD(L)1 has come to the promising outcomes, and clinical trials are under way in order to use agents with bifunctional capacity and fusion proteins for bonding TGF-β traps with anti-PD-L1 antibodies aiming at reinvigorating immune responses and promoting persistent responses against advanced stage cancers, especially tumours with immunologically cold ecosystem.